A BARF1-specific mAb as a new immunotherapeutic tool for the management of EBV-related tumors.

Détails

Ressource 1Télécharger: koni-06-04-1304338 (1).pdf (1017.58 [Ko])
Etat: Serval
Version: Final published version
ID Serval
serval:BIB_8CBC1FEC9495
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A BARF1-specific mAb as a new immunotherapeutic tool for the management of EBV-related tumors.
Périodique
Oncoimmunology
Auteur(s)
Turrini R., Merlo A., Martorelli D., Faè D.A., Sommaggio R., Montagner I.M., Barbieri V., Marin O., Zanovello P., Dolcetti R., Rosato A.
ISSN
2162-4011 (Print)
ISSN-L
2162-4011
Statut éditorial
Publié
Date de publication
2017
Peer-reviewed
Oui
Volume
6
Numéro
4
Pages
e1304338
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
The use of monoclonal antibodies (mAb) for the diagnosis and treatment of malignancies is acquiring an increasing clinical importance, thanks to their specificity, efficacy and relative easiness of use. However, in the context of Epstein-Barr virus (EBV)-related malignancies, only cancers of B-cell origin can benefit from therapeutic mAb targeting specific B-cell lineage antigens. To overcome this limitation, we generated a new mAb specific for BARF1, an EBV-encoded protein with transforming and immune-modulating properties. BARF1 is expressed as a latent protein in nasopharyngeal (NPC) and gastric carcinoma (GC), and also in neoplastic B cells mainly upon lytic cycle induction, thus representing a potential target for all EBV-related malignancies. Considering that BARF1 is largely but not exclusively secreted, the BARF1 mAb was selected on the basis of its ability to bind a domain of the protein retained at the cell surface of tumor cells. In vitro, the newly generated mAb recognized the target molecule in its native conformation, and was highly effective in mediating both ADCC and CDC against BARF1-positive tumor cells. In vivo, biodistribution analysis in mice engrafted with BARF1-positive and -negative tumor cells confirmed its high specificity for the target. More importantly, the mAb disclosed a relevant antitumor potential in preclinical models of NPC and lymphoma, as evaluated in terms of both reduction of tumor masses and long-term survival. Taken together, these data not only confirm BARF1 as a promising target for immunotherapeutic interventions, but also pave the way for a successful translation of this new mAb to the clinical use.

Pubmed
Web of science
Création de la notice
23/05/2017 17:26
Dernière modification de la notice
03/03/2018 19:14
Données d'usage